Total astragalosides decrease apoptosis and pyroptosis by inhibiting enterovirus 71 replication in gastric epithelial cells

Zhang,Xiaoyan; Hao,Jinfang; Sun,Chenxi; Du,Jianping; Han,Qian; Li,Qingshan

doi:10.3892/etm.2022.11162

Total astragalosides decrease apoptosis and pyroptosis by inhibiting enterovirus 71 replication in gastric epithelial cells

Authors:
- Xiaoyan Zhang
- Jinfang Hao
- Chenxi Sun
- Jianping Du
- Qian Han
- Qingshan Li
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Affiliations: Department of Laboratory Medicine of Fenyang College, School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China
Published online on: January 24, 2022 https://doi.org/10.3892/etm.2022.11162
Article Number: 237
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Enterovirus 71 (EV71) is one of the primary pathogens involved in severe hand, foot and mouth disease in children. EV71 infection causes various types of programmed cell death. However, there are currently no clinically approved specific antiviral drugs for control of EV71 infection. Astragalus membranaceus (AM), a Traditional Chinese medicine, has been used in antiviral therapy in China. The aim of the present study was to determine whether total astragalosides (ASTs), bioactive components of AM, protect against EV. DAPI nuclear staining was used to observe morphological changes of the nucleus and the protective effect of ASTs, which revealed that the nucleus shrank following EV71 infection, while ASTs reversed it. Cell Counting Kit‑8 assay found that human normal gastric epithelial cell (GES‑1 cell) viability decreased following EV71 infection, while lactate dehydrogenase (LDH) assay showed that EV71 infection induced GES‑1 cell damage. Western blotting was used to measure the expression levels of apoptosis and pyroptosis marker protein to determine whether EV71 infection induced apoptosis and pyroptosis in GES‑1 cells. Reverse transcription‑quantitative PCR was used to determine the anti‑EV71 effect of ASTs. The results showed that ASTs protected GES‑1 cells from EV71‑induced cell apoptosis and pyroptosis. Furthermore, the present data demonstrated that the protective effect of ASTs was exerted by suppressing EV71 replication and release. These findings suggested that ASTs may represent a potential antiviral agent for the treatment of EV71 infection.

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1	Gao W, Hou M, Liu X, Li Z, Yang Y and Zhang W: Induction of SOCS expression by EV71 infection promotes EV71 replication. Biomed Res Int. 2020(2430640)2020.PubMed/NCBI View Article : Google Scholar
2	Fu M, Bai J, Gao S, Chang Z, Zhou X and Long JE: Construction and characterization of an infectious cDNA clone of enterovirus 71: A rapid method for rescuing infectious virus based on stable cells expressing T7 polymerase. Arch Virol. 166:627–632. 2021.PubMed/NCBI View Article : Google Scholar
3	Hu Y, Xu Y, Huang Z, Deng Z, Fan J, Yang R, Ma H, Song J and Zhang Y: Transcriptome sequencing analysis of SH-SY5Y cells infected with EV71 reveals the potential neuropathic mechanisms. Virus Res. 282(197945)2020.PubMed/NCBI View Article : Google Scholar
4	Fu Y, Zhang L, Zhang F, Tang T, Zhou Q, Feng C, Jin Y and Wu Z: Exosome-mediated miR-146a transfer suppresses type I interferon response and facilitates EV71 infection. PLoS Pathog. 13(e1006611)2017.PubMed/NCBI View Article : Google Scholar
5	Ampomah PB and Lim LHK: Influenza A virus-induced apoptosis and virus propagation. Apoptosis. 25:1–11. 2020.PubMed/NCBI View Article : Google Scholar
6	Xie WH, Ding J, Xie XX, Yang XH, Wu XF, Chen ZX, Guo QL, Gao WY, Wang XZ and Li D: Hepatitis B virus X protein promotes liver cell pyroptosis under oxidative stress through NLRP3 inflammasome activation. Inflamm Res. 69:683–696. 2020.PubMed/NCBI View Article : Google Scholar
7	Hu X, Jiang J, Ni C, Xu Q, Ye S, Wu J, Ge F, Han Y, Mo Y, Huang D and Yang L: HBV integration-mediated cell apoptosis in HepG2.2.15. J Cancer. 10:4142–4150. 2019.PubMed/NCBI View Article : Google Scholar
8	Wang Y, Qin Y, Wang T, Chen Y, Lang X, Zheng J, Gao S, Chen S, Zhong X, Mu Y, et al: Pyroptosis induced by enterovirus 71 and coxsackievirus B3 infection affects viral replication and host response. Sci Rep. 8(2887)2018.PubMed/NCBI View Article : Google Scholar
9	Ding Q, Zhang W, Cheng C, Mo F, Chen L, Peng G, Cai X, Wang J, Yang S and Liu X: Dioscin inhibits the growth of human osteosarcoma by inducing G2/M-phase arrest, apoptosis, and GSDME-dependent cell death in vitro and in vivo. J Cell Physiol. 235:2911–2924. 2020.PubMed/NCBI View Article : Google Scholar
10	Karam JA, Lotan Y, Karakiewicz PI, Ashfaq R, Sagalowsky AI, Roehrborn CG and Shariat SF: Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol. 8:128–136. 2007.PubMed/NCBI View Article : Google Scholar
11	Häcker G: The morphology of apoptosis. Cell Tissue Res. 301:5–17. 2000.PubMed/NCBI View Article : Google Scholar
12	Wyllie AH, Kerr JF and Currie AR: Cell death: The significance of apoptosis. Int Rev Cytol. 68:251–306. 1980.PubMed/NCBI View Article : Google Scholar
13	Song F, Yu X, Zhong T, Wang Z, Meng X, Li Z, Zhang S, Huo W, Liu X, Zhang Y, et al: Caspase-3 inhibition attenuates the cytopathic effects of EV71 infection. Front Microbiol. 9(817)2018.PubMed/NCBI View Article : Google Scholar
14	Cookson BT and Brennan MA: Pro-inflammatory programmed cell death. Trends Microbiol. 9:113–114. 2001.PubMed/NCBI View Article : Google Scholar
15	Brennan MA and Cookson BT: Salmonella induces macrophage death by caspase-1-dependent necrosis. Mol Microbiol. 38:31–40. 2000.PubMed/NCBI View Article : Google Scholar
16	Gaul S, Leszczynska A, Alegre F, Kaufmann B, Johnson CD, Adams LA, Wree A, Damm G, Seehofer D, Calvente CJ, et al: Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis. J Hepatol. 74:156–167. 2021.PubMed/NCBI View Article : Google Scholar
17	Duan G, Yang H, Shi L, Sun W, Sui M, Zhang R, Wang X, Wang F, Zhang W, Xi Y and Fan Q: Serum inflammatory cytokine levels correlate with hand-foot-mouth disease severity: A nested serial case-control study. PLoS One. 9(e112676)2014.PubMed/NCBI View Article : Google Scholar
18	Han J, Wang Y, Gan X, Song J, Sun P and Dong XP: Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease. J Med Virol. 86:1377–1385. 2014.PubMed/NCBI View Article : Google Scholar
19	James DS: The multisystem adverse effects of NSAID therapy. J Am Osteopath Assoc. 99 (Suppl 11):S1–S7. 1999.PubMed/NCBI
20	Polderman JA, Farhang-Razi V, Van Dieren S, Kranke P, DeVries JH, Hollmann MW, Preckel B and Hermanides J: Adverse side effects of dexamethasone in surgical patients. Cochrane Database Syst Rev. 8(CD011940)2018.PubMed/NCBI View Article : Google Scholar
21	Zhang X, Liang T, Yang W, Zhang L, Wu S, Yan C and Li Q: Astragalus membranaceus injection suppresses production of interleukin-6 by activating autophagy through the AMPK-mTOR pathway in lipopolysaccharide-stimulated macrophages. Oxid Med Cell Longev. 2020(1364147)2020.PubMed/NCBI View Article : Google Scholar
22	Sai YP, Song YC, Chen XX, Luo X, Liu J and Cui WJ: Protective effect of astragalosides from radix astragali on adriamycin-induced podocyte injury. Exp Ther Med. 15:4485–4490. 2018.PubMed/NCBI View Article : Google Scholar
23	OuYang Y, Huang J, OuYang Z and Kang J: Enrichment and purification process of astragalosides and their anti-human gastric cancer MKN-74 cell proliferation effect. Afr Health Sci. 14:22–27. 2014.PubMed/NCBI View Article : Google Scholar
24	Li X, He D, Zhang L, Cheng X, Sheng B and Luo Y: A novel antioxidant agent, astragalosides, prevents shock wave-induced renal oxidative injury in rabbits. Urol Res. 34:277–282. 2006.PubMed/NCBI View Article : Google Scholar
25	Li C, Yang F, Liu F, Li D and Yang T: NRF2/HO-1 activation via ERK pathway involved in the anti-neuroinflammatory effect of astragaloside IV in LPS induced microglial cells. Neurosci Lett. 666:104–110. 2018.PubMed/NCBI View Article : Google Scholar
26	Cheng JH, Sun YJ, Zhang FQ, Zhang XR, Qiu XS, Yu LP, Wu YT and Ding C: Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response. Sci Rep. 6(24721)2016.PubMed/NCBI View Article : Google Scholar
27	Li Q, Cheng F, Zhou K, Fang L, Wu J, Xia Q, Cen Y, Chen J and Qing Y: Increased sensitivity to TNF-α promotes keloid fibroblast hyperproliferation by activating the NF-κB, JNK and p38 MAPK pathways. Exp Ther Med. 21(502)2021.PubMed/NCBI View Article : Google Scholar
28	Xu T, Li Y, Wu HL, Chen H, Wu H, Guo M, Zhao M, Wang C, Lin T, Lin Z, et al: The inhibition of enterovirus 71 induced apoptosis by durvillaea antarctica through P53 and STAT1 signaling pathway. J Med Virol. 93:3532–3538. 2021.PubMed/NCBI View Article : Google Scholar
29	You L, Chen J, Liu W, Xiang Q, Luo Z, Wang W, Xu W, Wu K, Zhang Q, Liu Y and Wu J: Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation. Virulence. 11:537–553. 2020.PubMed/NCBI View Article : Google Scholar
30	Ma JQ, Sun YZ, Ming QL, Tian ZK, Yang HX and Liu CM: Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-β1/Smad3 and autophagy pathway. Int Immunopharmacol. 77(105984)2019.PubMed/NCBI View Article : Google Scholar
31	Wang CY, Huang SC, Zhang Y, Lai ZR, Kung SH, Chang YS and Lin CW: Antiviral ability of Kalanchoe gracilis leaf extract against enterovirus 71 and coxsackievirus A16. Evid Based Complement Alternat Med. 2012(503165)2012.PubMed/NCBI View Article : Google Scholar
32	Zhang W, Qiao H, Lv Y, Wang J, Chen X, Hou Y, Tan R and Li E: Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors. PLoS One. 9(e110429)2014.PubMed/NCBI View Article : Google Scholar
33	Wang M, Dong Q, Wang H, He Y, Chen Y, Zhang H, Wu R, Chen X, Zhou B, He J, et al: Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits Enterovirus 71 reproduction through downregulation of ERp57. Oncotarget. 7:8797–8808. 2016.PubMed/NCBI View Article : Google Scholar
34	Li X, Liu Y, Wu T, Jin Y, Cheng J, Wan C, Qian W, Xing F and Shi W: The antiviral effect of baicalin on enterovirus 71 in vitro. Viruses. 7:4756–4771. 2015.PubMed/NCBI View Article : Google Scholar
35	Jiao XY, Guo L, Huang DY, Chang XL and Qiu QC: Distribution of EV71 receptors SCARB2 and PSGL-1 in human tissues. Virus Res. 190:40–52. 2014.PubMed/NCBI View Article : Google Scholar
36	Cao L and Zhang X, Yuan S, Cheng K and Zhang X: Autophagy induced by enterovirus 71 regulates the production of IL-6 through the p38MAPK and ERK signaling pathways. Microb Pathog. 131:120–127. 2019.PubMed/NCBI View Article : Google Scholar
37	Li H, Bai Z, Li C, Sheng C and Zhao X: EV71 infection induces cell apoptosis through ROS generation and SIRT1 activation. J Cell Biochem. 121:4321–4331. 2020.PubMed/NCBI View Article : Google Scholar
38	Guo X, Liu WL, Yang D, Shen ZQ, Qiu ZG, Jin M and Li JW: Hepatitis C virus infection induces endoplasmic reticulum stress and apoptosis in human fetal liver stem cells. J Pathol. 248:155–163. 2019.PubMed/NCBI View Article : Google Scholar
39	Iannello A, Debbeche O, Martin E, Attalah LH, Samarani S and Ahmad A: Viral strategies for evading antiviral cellular immune responses of the host. J Leukoc Biol. 79:16–35. 2006.PubMed/NCBI View Article : Google Scholar
40	Guo XJ and Thomas PG: New fronts emerge in the influenza cytokine storm. Semin Immunopathol. 39:541–550. 2017.PubMed/NCBI View Article : Google Scholar
41	Shao P, Wu X, Li H, Wu Z, Yang Z and Yao H: Clinical significance of inflammatory cytokine and chemokine expression in hand, foot and mouth disease. Mol Med Rep. 15:2859–2866. 2017.PubMed/NCBI View Article : Google Scholar
42	Zhuo L, Chen X, Sun Y, Wang Y, Shi Y, Bu L, Xia W, Han J, Chen D and Li X: Rapamycin inhibited pyroptosis and reduced the release of IL-1β and IL-18 in the septic response. Biomed Res Int. 2020(5960375)2020.PubMed/NCBI View Article : Google Scholar
43	Kruse RH, Puckett WH and Richardson JH: Biological safety cabinetry. Clin Microbiol Rev. 4:207–241. 1991.PubMed/NCBI View Article : Google Scholar